Inhibition of protease-ENaC signaling improves mucociliary function in cystic fibrosis airways

Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.

Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.

Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.

Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.

Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.

The perception of woman on the example of the Odyssey of Homer and its english translation by James Huddleston and portuguese translation by Frederico Lourenço

Dissertação de mestrado, Estudos Literários e Artísticos, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015

Evaluation of outpatient child-adolescent mental health services (CAMHS) in Attica-Greece

ABSTRACT: Background: Childhood is a critical time for social and emotional development, educational progress and mental health prevention. Mental health for children and adolescents is defined by the achievement of expected developmental, cognitive, social and emotional skills. The development of child-adolescent mental health services (CAMHS) is a necessity for each country, not only as a prevention measure for the wellbeing of people, but also as an investment to the future of countries. Qualitative evaluation of services is the only way to ensure whether services function under quality standards and increase the possibility of better outcomes for their patients. This study examines the greek outpatient CAMHS against the British Standards of National Institute of Excellence for community CAMHS. The Standards assessed refer to the areas of Assessment, Care and Intervention. Objectives: The main objectives of the study are 1) to evaluate Greek outpatient CAMHS in the Attica region 2) to promote the evaluation process for mental health services in Greece. Methods: Due to the fact that Greek services are based on the British model, the tool used was the British self-review questionnaire of Quality Network for Community CAMHS(QNCC).The tool was translated, adapted and posted to services. Twelve out of twenty outpatient CAMHS of Attica (including Athens) responded. Data was collected and performed by the Statistical Package for Social Sciences SPSS. Results: The study resulted that the CAMHS examined, meet moderately the British Standards of 1) Referral and Access, 2) Assessment & Care planning, 3) Care & Intervention. Two out of twelve services examined, meet the standards of "Assessment and Care" in a higher percentage between 75% and 100%. Conclusions: The paper describes a satisfactory function of CAMHS in Attica prefecture taking into consideration the extremely difficult political situation of Greece at the time of the research. Strong and weak domains are identified. Also the translation and adaptation of British tools promote the evaluation process and quality assurance of Greek CAMHS.

Le chevalier de Saint-Jean. Tome 2 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 3 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 1 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

Le chevalier de Saint-Jean. Tome 4 / , traduit de l'anglais, de Miss Porter, par Jean Cohen

Titre original : The knight of St. John

An analysis of Ibn al-'Arabi's al-Insan al-Kamil, the Perfect Individual, with a brief comparison to the thought of Sir Muhammad Iqbal

This thesis analyzes four philosophical questions surrounding Ibn al-'Arabi's concept of the al-iman al-kamil, the Perfect Individual. The Introduction provides a definition of Sufism, and it situates Ibn al-'Arabi's thought within the broader context of the philosophy of perfection. Chapter One discusses the transformative knowledge of the Perfect Individual. It analyzes the relationship between reason, revelation, and intuition, and the different roles they play within Islam, Islamic philosophy, and Sufism. Chapter Two discusses the ontological and metaphysical importance of the Perfect Individual, exploring the importance of perfection within existence by looking at the relationship the Perfect Individual has with God and the world, the eternal and non-eternal. In Chapter Three the physical manifestations of the Perfect Individual and their relationship to the Prophet Muhammad are analyzed. It explores the Perfect Individual's roles as Prophet, Saint, and Seal. The final chapter compares Ibn al-'Arabi's Perfect Individual to Sir Muhammad Iqbal's in order to analyze the different ways perfect action can be conceptualized. It analyzes the relationship between freedom and action.

Memorandum - Report on operations of 1st Division against St. Mihiel Salient, 1918

A memorandum describing the days leading up to the Battle of Saint-Mihiel. The document describes 1. Statement of Operation, 2. Character of Terrain, 3. Initial Dispositions, 4. Suitability of Formations, 5. How such formations were, or could have been, best adapted to meet the changing conditions of combat and terrain, 6. Employment of Infantry Weapons, 7. Artillery Support, 8. Passage of Obstacles, 9. Passage of Lines, 10. Destruction of Opposition, 11. Fighting in Intermediate Zone, 12. Organization of Ground, 13. Liaison, 14. General Observations.